Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The promoter region for transcription of the 3.6-kilobase mRNA of hepatitis B virus was identified by the chloramphenicol acetyltransferase assay by using HuH-7 hepatoma cells and was found to function directly in virus production by way of the transient expression system of HBV. The 5'-upstream sequence from nucleotides 1573 to 1657 (the transcription start site) was indispensable for promoter function, while the AT-rich sequence (from nucleotides 1581 to 1604) containing a directly repeated sequence TGTT connecting the same flanking sequence PyAAAGAC (where Py is a pyrimidine) at both sides was an essential element within this promoter region. A specific cellular factor which interacted with the essential element was detected in the HuH-7 cell extract. A similar binding factor was also observed in HepG2 and huH2-2 hepatoma cells. This factor may thus be responsible for regulating 3.6-kilobase mRNA, pregenome RNA transcription, or both.
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PMID:Identification of a promoter region for 3.6-kilobase mRNA of hepatitis B virus and specific cellular binding protein. 254 3

An 88-base pair fragment in the core promoter of the human hepatitis B virus (HBV) contains a functional promoter and a strong liver-specific enhancer. This enhancer functions in human hepatoma cells, where it is much more active than the previously described HBV enhancer in stimulating expression of the linked bacterial chloramphenicol acetyltransferase gene expressed from heterologous promoters. Studies of the role of this enhancer-promoter in HBV may help to clarify mechanisms of gene expression in cells infected with HBV and the role of the virus in the pathogenesis of hepatitis and hepatocellular carcinoma.
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PMID:A liver-specific enhancer in the core promoter region of human hepatitis B virus. 255 95

The rat glucokinase (GK) gene containing the first exon was isolated and its 5' flanking region was characterized by the bacterial chloramphenicol acetyltransferase (CAT) assay. A transient expression assay with a series of 5' deletion constructs (-5.5 k to -48) of GK-CAT fusion genes indicated that the 5' flanking sequence up to nucleotide -87 was sufficient for promoter activity in adult rat hepatocytes, but its activity was much weaker than that of the SV40 enhancer/promoter. Similar promoter activity was also detected in dRLh-84 hepatoma cells, which do not express glucokinase. Insulin treatment caused no change in the CAT activity of hepatocytes transfected with the fusion genes. These results suggest that the 5' flanking region of the glucokinase gene up to -5.5 k does not contain enhancer elements responsible for tissue-specific expression or insulin regulation.
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PMID:Characterization of the 5' flanking region of rat glucokinase gene. 259 Feb

The outer envelope of the 42-nm virion of the human hepatitis B virus (HBV) is composed of the large, the middle, and the major surface proteins. Whereas the middle and the major surface proteins are transcribed from the SPII promoter of the pre-S/S gene, the large surface protein is transcribed from the SPI promoter located upstream of SPII. We have previously shown that transcription of SPI (comprising nucleotides [nt] -380 to +17) occurs preferentially in differentiated hepatoma cell lines (H.K. Chang and L.P. Ting, Virology 170:176-183, 1989). In this report, we further demonstrated that a sequence of 95 base pairs in the upstream region of SPI (nt -95 to +17) was necessary and sufficient for such preferential expression in differentiated hepatoma cells. By analysis of the expression of the chloramphenicol acetyltransferase gene in a series of mutants with deletions at the 5' end of SPI, we identified a positive transcriptional cis-acting element mapping at nt -95 to -72 which appears to play a key role in the regulation of the expression of the large surface protein. This region shared a high degree of sequence homology with regulatory sequences of several liver-specific genes from human, mouse, and rat, with a consensus sequence (G/A)GTTA(A/C)TNNT(C/T)NNC(A/C). We further identified a nuclear factor present in the nuclear extracts of differentiated human hepatoma cell lines which interacted specifically with this element of the SPI promoter. This nuclear factor was similar to the rat liver-specific factor HNF-1, since an oligonucleotide containing the recognition sequence of HNF-1 could efficiently compete for the human factor in a footprinting assay. The sequence at nt -93 to -68 which was bound by this factor in SPI was termed the HNF-1-binding element. Activation of the SPI promoter by human differentiated hepatocyte nuclear factor 1, described in this report, probably explains, first, the formation of the 42-nm virion specifically in liver but not in several other tissues despite the synthesis of the middle and the major surface proteins in those tissues, and second, why only differentiated hepatoma cell lines are able to produce 42-nm-like virion particles on transfection by HBV DNA.
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PMID:A liver-specific nuclear factor interacts with the promoter region of the large surface protein gene of human hepatitis B virus. 260 16

Regulation of albumin gene expression is believed to be mediated by multiple nuclear factors that interact with cis-acting DNA sequences within the first 160 base pairs (bp) of the promoter. The minimal promoter sequence required to generate tissue-specific expression has not been clearly defined. We have constructed a series of transient expression vectors containing progressive deletions of the mouse albumin gene 5'-flanking sequence fused to the bacterial chloramphenicol acetyltransferase (CAT) gene and include the Moloney murine leukemia viral (Mo-MuLV) enhancer. Promoter activity was determined in mouse hepatoma and fibroblast cell lines by chloramphenicol acetyltransferase and S1 nuclease analyses. All constructions were compared with -623 Albcat-Mo-MuLV which contains all the sequence homology between the rat and mouse promoters. Low levels of expression were observed with -60 Albcat-Mo-MuLV (10%) in hepatoma but not fibroblast cells. Addition of promoter sequence to -208 bp progressively increased activity to 190% in the hepatoma cells, while -308 and -1612 Albcat-Mo-MuLV had activity similar to the -623 Albcat-Mo-MuLV level, and -3000 Albcat-Mo-MuLV showed a 2-fold reduction in transcriptional activity. The inclusion of promoter sequences upstream of -60 generated low levels of expression in the fibroblasts. We also show that factors from mouse liver nuclear extracts protect at least five regions of the albumin promoter upstream of -160. Our results indicate that tissue specificity is established within the proximal promoter region and that additional cis-acting elements that may have a functional role in the efficiency of albumin gene expression are located upstream of -160 bp.
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PMID:Cell-specific expression of mouse albumin promoter. Evidence for cell-specific DNA elements within the proximal promoter region and cis-acting DNA elements upstream of -160. 272 22

We analyzed the function of a DNA domain located upstream of the cytochrome P450IA1 gene in wild-type (Hepa 1c1c7) mouse hepatoma cells and in high-activity variant (HAV) cells that overtranscribe the gene in response to the inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Transfection experiments indicated that both wild-type and HAV DNA confer responsiveness to TCDD upon the bacterial chloramphenicol acetyltransferase (CAT) gene. However, the level of CAT activity was four- to fivefold higher when the hybrid genes were expressed in the HAV cells. These findings imply that an alteration in a trans-acting function confers the HAV phenotype. Studies of mRNA accumulation imply that TCDD acts by enhancing the rate of mRNA initiation rather than by removing a block in mRNA elongation. We found that both wild-type and HAV cells used the same transcriptional promoter as that described previously for the cytochrome P450IA1 gene in C57BL/6 mouse liver. Both cell types exhibited superinduction of cytochrome P450IA1 gene expression in response to TCDD plus cycloheximide.
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PMID:Activation of cytochrome P450IA1 gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin in wild-type and high-activity variant mouse hepatoma cells. 273 Jul 63

The role of the hepatitis B virus (HBV) X gene during virus infection has not been defined. We previously showed that expression of the HBV X gene in the human hepatocellular carcinoma cell line HepG2 trans-activates chloramphenicol acetyltransferase gene expression under control of the human immunodeficiency virus 1 (HIV-1) long terminal repeat and we have now identified a specific sequence in the HIV-1 long terminal repeat that is responsive to the HBV X gene. Plasmid constructs with the chloramphenicol acetyltransferase gene regulated by an isolated and twice-repeated 12-base-pair HIV-1 enhancer sequence homologous to the nucleotide sequence that binds the nuclear transcription factor NF-kappa B (the HIV-1 kappa B-like sequence) were trans-activated by the HBV X gene in HepG2 cells, indicating that the kappa B-like enhancer sequence in the HIV-1 long terminal repeat is responsive to the X gene. When eight copies of the HIV-1 kappa B-like sequence were used to regulate beta-globin gene expression, transcription of this gene was activated by the HBV X gene in HepG2 cells and no beta-globin gene transcription was detected in the absence of the HBV X gene. beta-globin gene expression regulated by the activator protein 2 (AP-2) binding sequence was not activated by the HBV X gene. Treatment of HepG2 cells with phorbol ester resulted in modest activation of the HIV-1 kappa B-like enhancer sequence suggesting that an NF-kappa B-like factor was induced in these cells as it is in T lymphocytes by phorbol ester; however, phorbol ester did not demonstrably enhance the activation of the HIV-1 enhancer observed with the HBV X gene. These experiments indicate that the HIV-1 kappa B-like transcriptional enhancer sequence is activated by the HBV X gene and suggest that the HBV X gene might play a role in regulating transcription of a gene under control of a kappa B-like enhancer during HBV infection. Since such a sequence has not been found in the HBV genome and HBV gene expression appears not to be regulated by the HBV X gene, a cellular gene that plays a role in HBV replication could be the target of the X gene during HBV infection.
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PMID:Hepatitis B virus X gene activates kappa B-like enhancer sequences in the long terminal repeat of human immunodeficiency virus 1. 274 Mar 49

The synthesis of the glutathione S-transferase Ya subunit is induced in the mammalian liver by chemicals such as phenobarbital and 3-methylcholanthrene. To study the mechanism of this induction, the 5'-flanking region of a mouse glutathione S-transferase Ya subunit gene was fused to the structural gene for chloramphenicol acetyltransferase. The fusion gene was introduced into hepatoma cells for the assay of the expressed acetyltransferase activity. At least two cis-regulatory elements were identified in the 5'-flanking region of the Ya gene: one, responsible for the basal level of expression, is present in the sequence up to -0.2 kb; another, responsible for the inducible expression by aromatic compounds such as beta-naphthoflavone and 3-methylcholanthrene, is located in the sequence from -0.2 kb to -1.6 kb. The inducible element was functional only in cells with normal aromatic compound receptors, and it retained responsiveness to beta-naphthoflavone when transfected into homologous (mouse) or heterologous (rat, human) hepatoma cells. A 150-bp region upstream from the transcription initiation site of the mouse Ya gene was investigated for cis-acting transcriptional elements that are recognized by specific DNA-binding proteins. We show by DNase I foot-printing assays using extracts from liver nuclei that the Ya gene promoter contains, in addition to the TATA and CCAAT boxes, a more distal element that binds a protein which is probably related to the family of nuclear factor 1 (NF1).
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PMID:Regulatory elements controlling the basal and drug-inducible expression of glutathione S-transferase Ya subunit gene. 277 26

The multihormonal regulation of phosphoenolpyruvate carboxykinase (PEPCK) was studied using chimeric genes composed of various regions of the PEPCK gene promoter region fused to the coding sequence of the chloramphenicol acetyltransferase (CAT) gene. These constructions, transfected into H4IIE hepatoma cells, are regulated like the endogenous PEPCK gene: dexamethasone and cAMP both stimulate PEPCK-CAT gene expression and their effects are additive; insulin inhibits the individual or combined effects of these stimulatory agents; and insulin inhibits dexamethasone-stimulated PEPCK-CAT fusion gene expression in a concentration-dependent fashion that is half-maximal at 10(-11) M. The induction by dexamethasone and the inhibition by insulin is specific for the DNA sequences that flank the 5' end of the PEPCK gene because similar effects were not observed for a plasmid in which the promoter and enhancer sequences of simian virus 40 (SV40) are fused to CAT. These results imply that the DNA adjacent to the transcription start site of the PEPCK gene contains the cis-acting hormone response elements responsible for the multihormonal regulation of this gene, including the insulin response.
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PMID:Multihormonal regulation of phosphoenolpyruvate carboxykinase-chloramphenicol acetyltransferase fusion genes. Insulin's effects oppose those of cAMP and dexamethasone. 282 6

Upstream sequences of the human P450IA1 gene were inserted into a promoterless expression vector (pSVO-cat) containing the chloramphenicol acetyltransferase (CAT) gene, with and without the Harvey murine sarcoma virus (Ha-MSV) core enhancer, and either plasmid was transfected into human breast carcinoma MCF-7 and MDA-231 and mouse hepatoma Hepa-1 cell lines. In most instances constitutive and inducible CAT activities in the transient CAT expression assay were similar (within 3-fold) to those in the stable transformation CAT assay (selection of G418-resistant colonies following co-transfection with pSV2-neo). In the case of Ha-MSV-containing constructs stably integrated in the two human breast cancer lines, however, CAT expression was more than two orders of magnitude greater than that transiently expressed in these cells. Since the major difference between these two assays is plasmid copy number, these data suggest the presence of limiting amounts of tissue-specific positive-control enhancer-binding factor(s) in the breast carcinoma cell lines.
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PMID:Human P45IA1 upstream regulatory sequences expressing the chloramphenicol acetyltransferase gene. Effect of Ha-MSV enhancer and comparison of transient with stable transformation assays. 282 73


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